Cochlear implants stimulate the auditory nerve using stimuli that minimize the release of toxic electrochemical byproducts and damage associated with metabolic stress of the stimulated neurons. However, these guidelines were based on acute stimulation of cortical neurons and thus do not reflect the safe levels of stimulation for us in a cochlear implant. This application will establish safe stimulation limits specifically for cochlear implants using chronic electrical stimulation. The project will use clinical implants and electrode fabrication technology to manufacture customized electrode arrays for this research with carefully defined surfaces as small as 0.05 mm2. We hypothesize that safe stimulation levels will be significantly greater than the present levels defined by acute studies. If this hypothesis is correct the next generation of cochlear implants could include smaller electrodes and new stimulation strategies leading to improved clinical outcomes for cochlear implant users. This project has three specific aims: i) establish the threshold stimulus levels for electrochemical damage using platinum electrodes. In this study stimulus rate and charge per phase will be held constant while charge density will be varied from 100-400 C/cm2/phase using purpose built electrode arrays. The prime measures used to evaluate the extent of electrochemical damage will be the degree of tissue response in stimulated versus control cochleae, neural survival and evidence of electrode degradation; ii) establish the threshold stimulus parameters giving rise to metabolic damage following chronic electrical stimulation of the auditory nerve. This study will co-vary charge per phase (0.39-0.78 C/phase; i.e. from safe to the unsafe levels defined acutely), stimulation rate (250 - 1000 pulses per second) and duty cycle (25 - 100%). These combinations will allow us to examine the effects of each parameter independently. Metabolic damage is expected to specifically target auditory neurons and therefore electrophysiological response properties and neural survival will be the primary measures to establish the extent of damage and to define safe limits in both chronically stimulated versus control cochleae; and iii) establish the interaction between electrochemical and metabolic damage by co-varying charge density, charge per phase, stimulation rate and duty cycle around the safe / unsafe boundaries determined in aims i) and ii). These results will allow us to determine the extent of interaction, if any, between the electrochemical and metabolic damage, again impacting on safe stimulation levels.